Study paves way for targeted therapy of periodontitis
HALLE (SAALE)/LEIPZIG, Germany: A new approach to the treatment of periodontitis could make the use of antibiotics obsolete, as it targets only the bacteria that cause the disease while sparing those that are harmless. It has been developed as a result of a collaboration between the Martin Luther University Halle-Wittenberg (MLU), the Fraunhofer Institute for Cell Therapy and Immunology IZI in Leipzig and PerioTrap Pharmaceuticals in Halle. The researchers expect the new method of treatment to cause few side effects.
To date, the treatment of periodontitis has mainly involved the use of broad-spectrum antibiotics that combat all the bacteria in the oral cavity. However, according to one of the lead authors of the study, Dr Mirko Buchholz from PerioTrap Pharmaceuticals, this has some disadvantages. “One side effect of the treatment is that it also destroys all the harmless or beneficial bacteria in the oral cavity. In addition, the bacteria can ultimately develop resistance to the antibiotics,” he explained in an MLU press release.
In order to find a method of eliminating only the harmful bacteria, the research team developed a test substance that combats glutaminyl cyclase, a specific enzyme of the bacteria that plays an important role in metabolism. The underlying idea was that inactivating the enzyme would damage the bacteria and prevent the development of periodontitis.
The developed substance was tested for effectiveness in different clinics and universities in Switzerland, Poland and the US and was found to successfully suppress the growth of pathogenic bacteria.
Prof. Milton T. Stubbs, the other lead author of the study and a biotechnologist at MLU, explained the different variants of the researched enzyme: “Our target, glutaminyl cyclase, comes in two different variants. Normally, plants and bacteria have one variant of the enzyme and mammals another. The two variants work in a similar fashion, but they differ significantly in their structure. It’s a bit like flat-tip versus Phillips screwdrivers.”
To the surprise of the researchers, the bacteria that cause periodontitis possess the mammalian variant of the enzyme. “This is crucial for our approach because it gives us a possible target so we only kill the pathogenic bacteria and leave the harmless ones intact,” said Buchholz. According to Stubbs, the research team found small but significant differences between the bacterial enzymes and the human variant. These differences are probably sufficient for the new substance not to affect the human enzymes, which is why only minor side effects are expected.
The researchers concluded that the study findings demonstrate that glutaminyl cyclase is a promising target for the development of drugs to be used in the treatment of periodontitis and associated diseases. Further in vitro and in vivo studies are necessary, and it may, therefore, take some years before the research results in a marketable drug.
The study, titled “Mammalian-like type II glutaminyl cyclases in Porphyromonas gingivalis and other oral pathogenic bacteria as targets for treatment of periodontitis”, was published online on 5 January 2021 in the Journal of Biological Chemistry, ahead of inclusion in an issue.